Subunit dissociation and reassociation leads to preferential crystallization of haemoglobin Bart's (γ₄) from solutions of human embryonic haemoglobin Portland (ζ₂γ₂) at low pH

A variety of human haemoglobins (Hbs) are produced at different stages of human development, including three embryonic Hbs, foetal Hb and adult Hb. All are heterotetramers. During crystallization experiments on human embryonic Hb Portland (ζ₂γ₂), it was discovered by crystallographic and biochemical analysis that the homotetramer Hb Bart's (γ₄) preferentially crystallizes from ζ₂γ₂ solutions below pH 5. This results from dissociation of Hb Portland into γ₂ dimers and ζ monomers and has interesting implications for subunit interactions and tetramer stability in Hbs. It also makes possible a full crystallographic analysis of Hb Bart's, which is of considerable medical significance because of its presence in the red blood cells of millions of people worldwide who suffer from α-­thalassaemia.